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The Mild N-Nitrosation ofSecondary Amines withTrichloro NitromethaneAyhan S. Demir a , Ali S. Mahasneh a , Hilal Aksoy a &Zuhal Gercek aa Middle East Technical University, Department ofChemistry, 06531, Ankara, TurkeyVersion of record first published: 23 Sep 2006.

To cite this article: Ayhan S. Demir , Ali S. Mahasneh , Hilal Aksoy & Zuhal Gercek(1992): The Mild N-Nitrosation of Secondary Amines with Trichloro Nitromethane,Synthetic Communications: An International Journal for Rapid Communication ofSynthetic Organic Chemistry, 22:18, 2607-2611

To link to this article: http://dx.doi.org/10.1080/00397919208021659

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SYNTHETIC COMMUNICATIONS, 22(18), 2607-261 1 (1992)

THE MILD N-NITROSATION OF SECONDARY AMINES WITH TRICHLORO NITROMETHANE

Ayhan S. Derni;. Ali S.Mahasneh. Hilal Aksoy, and Zuhal Gercek

Middla East Technical University Department of Chemistry 06531 Ankara - Turkey

SumrnaryFieaction of trichloronitromethane with secondary amine leads to the formation of corresponding carcinogeneous N-nitrosarnines under mild Conditions.

Trichloronitrornethane (also known as chloropicrin) has not until now enter into any chemical synthesis,since its discovery early this century due to its high toxicity.

Trichloronitromethane is used principalby as a repellent, fumigant, insediside, parasiticide, and

disinfectant'-''.

In this work we studied the reaction of trichloronitromethane with secondary amine.The reaction of amine with trichloronitromethane was reported first by Werner et al." They found that trichloronitromethane gave with amine, coloured addition compounds, which

resuked from the interaction of subsidiary valencies associated with the NO2 group with the N- atom.ln general ,it appeared that the production of colour,in the case of nitro cornpounds,is

always a consequence of the saturation of the subsidiary valencies of the NO, group.ln our work we found that the reaction of trichloronitrornethane with secondaly amine in RT affords the nitrosation of amine (scheme 1) and we could not find this type of reaction in the literature.

CI,CNO, + R'$NH -> R'gN-NO

Scheme 1

*To whom correspondence should be addressed.

2607

Copyright 0 1992 by Marcel Dekker, Inc.

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2608 DEMIR ET AL.

Table 1 . N-nitrosation of amines &nine Reaction time (h) Product*'3 Yield %

Diisopropylamine 48

Morpholine 48 Piperidine 36 Diethylamine 48 Pyrrol id ine 36 t-Butyl-methylamine 24

Methyl-phenylamine 36

N-nitrosodiisopropyl- amine 52 N-nitrosomorpholine 46 N-nitrosopiperidine 58 N-nitrosodiethylamine 56 N-nitrosopyrrolidine 43 t-Butyl-methyl- nitrosamine 36 Methyl-phenyl- nitrosamine 48

'Products were characterised by comparison with authentic s ~ ~ ~ ~ ~ s ( I R , ~ H N MR,GLC)'~.

When trichloronitromethane and diisopropylamine were stirred at room temperature for two days

in acetonitrile as solvent a crystalline solid was forrned.After removing of the solid by fikration,and

remaining reaction mixture was evaporated,the crude product after chromatographic separation

gave an oil which was identitied as a N-nitrosodiisopropyl arnine ('H NMR, IR, MS) . We obtained

the same results (summarized in table 1) using different secondary amines. The only source of nitrosation in our reaction should be trichloronitromethane if one wants to

think about a reasonable explanation of what goes on.0n decomposition, trichloromethane was found to give phosgene and nitrosyl chloride according to scheme 2'1-15.

CI.$N02 - > Cl,C=O + ClNO

*$ O=N-Q-C-CI - > C12C=0 + ClNO -=.p

.CI

Scheme 2

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SECONDARY AMINES WITH TRICHLORO NITROMETHANE

RzNH t ClNO -> R2N-N0 + HCI

Scheme 3

2609

It is quite possible that nitrosyl chloride could be the nitrosation agent of the secondary amine as illustrated in scheme 3. The hydrogen chloride formed reacts with an equivalent amount of the amine to give the amine hydrochloride salt which was noted to separate out as a crystalline solid from the reaction mixture. Because the most nitrosamines are potently ~arcinogenic'~*'~ ,all of the produced nitrosamines were converted into hydrazine and amine using UH,Zn/HCI and TiCI, reductions"- ''. (NOTE,However,that most nltrosarnlnes are potent carclnogens and must be treated with due cautlon). To conclude, we have found that trichloromethane,which has a large area of use,converts amine

into carcinogeneous nitrosamines under mild conditions.

EXPERIMENTAL

Warnlng:Most nitrosamines are potentially carcinogenic,and should be handled,stored,and discarded with due caution for their toxic potential'6f'7.Trichloronitrcmethane produces severe sensory irritation in upper respiratory pwageslt has strong lacrimatory properties,produces

increased sensitivity of skin and eyes after frequent exposures. When taken orally,severe nausea, vomiting, colic, diarrhoea resus'. A# reagents were of commercial quality and reagent quality solvents were used without further purification.lR spectra were determined on a Phillips model PU9700.1H-NMR were determined on a Bruker AC 80 MHt FT spectrometer, m a s spectra were determined on a VG-TRIO-2 spectrometer.MeRing points were determined with a Buchi SMP-20 melting point apparatus and are uncorrected.Elementa1 analysis were performed at the Middle East Technical Univesity analysis center.

General procedure for the preparation of N-nltrOSO compounds.

Into a 100 mL flask 30 ml of dry acetonitrile were introduced.Dry nitrogen gas was bubbled trough the solvent and then 20 mrnd of amine and 10 mmol of trichloronitromethane were subsequently injected.The mixture was then stirred for 48 h at room temperature,during which white time. needle like crystals were formed. The crystals were separated from the reaction

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2610 DEMIR ET AL.

mirture by finration and were identified as a corresponding amine hydrochloride.From the

remaining liquid,the solvent was removed by evaporation and a light yellow crude liquid N-nitroso

amine was purified by chromatography and distillation(Kugelrohr).

Acknow1edgement:We thank the Middle East Technical Universrty for grant (No:AFP 1991) and

H.Aksoy tanks to Turkish Scientific Council (TUBITAK TBAG) for a fellowship.

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